Correlation between biopterin levels and intimal-media thickness in type-2 diabetic hypertensive patients.

BACKGROUND: Biopterins have a crucial role in the function of nitric oxide synthase, uncoupling of the enzyme leads to endothelial dysfunction and vascular damage, The aim of this study was to evaluate the relationship between the levels of biopterins with carotid intima-media thickness (CIMT) in hypertensive type-2 diabetic patients. METHODS: We studied 30 hypertensive type-2 diabetic patients and 30 normotensive non-diabetic age-matched subjects, in whom biopterins levels were measured by reverse phase high performance liquid chromatography with fluorescence detection. Additionally, the CIMT of both the common and internal carotid arteries was measured. The levels of biopterins and CIMT were correlated using the Pearson correlation coefficient test. RESULTS: We did not find a significantly correlation between biopterins levels and CIMT. However, we found a significantly inverse correlation between the BH4/BH2 ratio and the CIMT in patients (r = -0.54, p < 0.01). A multiple regression analysis revealed that the CIMT correlated significantly and independently with the BH4/BH2 ratio. CONCLUSION: Our results suggest that the BH4/BH2 ratio seems to be a better marker of vascular disease than biopterin levels.

Association between the levels of circulating adhesion molecules and biopterins in type-2 diabetic normotensive patients adhesion molecules and biopterins.

UNLABELLED: Endothelial dysfunction is a common feature in type-2 diabetic patients and is associated with inflammation, increased levels of circulating soluble adhesion molecules and atherosclerosis. Insufficiency of tetrahydrobiopterin leads to uncoupling of the nitric oxide synthase enzyme an endothelial dysfunction. THE AIM OF THIS STUDY: was to evaluate if there is a relationship between the levels of circulating soluble adhesion molecules and the levels of biopterins in normotensive type-2 diabetic patients. METHODS: We studied 30 normotensive type-2 diabetic patients in whom VCAM-1, ICAM-1 and E-selectin were measured by ELISA. Additionally, Biopterins were measured by reverse phase high performance liquid chromatography with fluorescence detection. The levels of circulating adhesion molecules and biopterins were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA. RESULTS: We did not find any relationship between absolute values of biopterins and soluble adhesion molecules. However, we observed significant inverse correlations between the BH4/BH2 ratio and VCAM-1 (r= -0.65, p<0.001) with ICAM-1 (r= -0.69, p<0.001) and with E-selectin (r=-0.64 p<0.001), CONCLUSION: Our data suggest that systemic levels of adhesion molecules have an inverse association with the BH4/BH2 ratio in type 2 diabetic normotensive patients.

Correlation between the levels of circulating adhesion molecules and atherosclerosis in hypertensive type-2 diabetic patients.

Endothelial dysfunction is a common feature in type-2 diabetic patients and in hypertension, and is associated with inflammation, increased levels of circulating soluble adhesion molecules, and atherosclerosis. The aim of this study was to evaluate the relationship between the levels of circulating soluble adhesion molecules and the degree of atherosclerosis in hypertensive type-2 diabetic patients. We studied 30 hypertensive type-2 diabetic patients in whom VCAM-1, ICAM-1, and E-selectin were measured by ELISA. Additionally, the intimal-medial thickness of both the common and internal carotid arteries was measured (B-mode ultrasound). The levels of circulating adhesion molecules and maximal carotid artery intimal-medial thicknesses were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA. We found significant correlations between ICAM-1 (r = 0.5) levels and maximal carotid artery intimal-medial thickness these patients. No correlation was observed with E-selectin and VCAM-1. Our results suggest that ICAM-1 is associated and correlated with the degree of atherosclerosis in type-2 diabetic hypertensive patients.

Is tetrahydrobiopterin a therapeutic option in diabetic hypertensive patients?

Nitric oxide (NO) is an important regulator of vascular tone, and is also an antithrombotic, anti-inflammatory, antiproliferative, and antiatherogenic factor. Endothelial function is altered in patients with coronary artery disease, stroke, and peripheral artery disease, and endothelial dysfunction correlates with the risk factor profile for a patient. Hypertension and type 2 diabetes are risk factors for vascular disease, and are both pathologies characterized by loss of NO activity. Indeed, endothelial dysfunction is usually present in diabetic and/or hypertensive patients. Tetrahydrobiopterin is an essential cofactor for the NO synthase enzyme, and insufficiency of this cofactor leads to uncoupling of the enzyme, release of superoxide, endothelial dysfunction, progression of hypertension, and finally, proatherogenic effects. Tetrahydrobiopterin is also an important mediator of NO synthase regulation in type 2 diabetes and hypertension, and may be a rational therapeutic target to restore endothelial function and prevent vascular disease in these patients. The aim of this paper is to review the rationale for therapeutic strategies directed to biopterins as a target for vascular disease in type 2 diabetic hypertensive patients.

Correlation between the levels of circulating adhesion molecules and atherosclerosis in type-2 diabetic normotensive patients: circulating adhesion molecules and atherosclerosis.

UNLABELLED: Endothelial dysfunction is a common feature in type-2 diabetic patients and is associated with inflammation, increased levels of circulating soluble adhesion molecules and atherosclerosis. The aim of this study was to evaluate the relationship between the levels of circulating soluble adhesion molecules and the degree of atherosclerosis in normotensive type-2 diabetic patients. RESULTS: We found significant correlations between ICAM-1 (r = 0.69, p < 0.001 95% IC 0.65 to 0.82) and VCAM-1 (r = 0.4, p < 0.03, 95% IC 0.65 to 0.82) levels and maximal carotid artery intimal-medial thickness, whereas no correlation was observed with E-selectin. METHODS: We studied 30 normotensive type-2 diabetic patients in whom VCAM-1, ICAM-1 and E-selectin were measured by ELISA. Additionally, the intimal-medial thickness of both the common and internal carotid arteries was measured (B-mode ultrasound). The levels of circulating adhesion molecules and maximal carotid artery intimal-medial thicknesses were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA. CONCLUSION: Our results suggest that ICAM-1 and VCAM-1 are markers associated, and correlated with the degree of atherosclerosis in normotensive type-2 diabetic patients.

Correlation between circulating adhesion molecule levels and albuminuria in type-2 diabetic hypertensive patients.

BACKGROUND/AIMS: Endothelial dysfunction, a common feature among hypertensive and type-2 diabetic patients, is associated with inflammation, increased levels of circulating soluble adhesion molecules (SAM), and urinary albumin excretion. The aim of this study was to evaluate the role of circulating SAM levels in the development of albuminuria in hypertensive type-2 diabetic patients. METHODS: We studied 30 hypertensive type-2 diabetic patients and 30 non-diabetic normotensive subjects, and measured their VCAM-1, ICAM-1 and E-selectin levels by ELISA, and their 24-hour urinary albumin excretion by nephelometry; the levels of circulating adhesion molecules and albuminuria were correlated with the Spearman correlation coefficient. RESULTS: We found that the diabetic patients had significantly (p < 0.001) higher levels of circulating SAM than control subjects. When levels of circulating SAM were correlated with albuminuria, we found a significant correlation between VCAM-1 levels and 24-hour urinary albumin excretion (r = 0.4, p < 0.02). CONCLUSION: Our results suggest that VCAM-1 may be a marker of nephropathy in hypertensive type-2 diabetic patients.

The effect of trandolapril and its fixed-dose combination with verapamil on circulating adhesion molecules levels in hypertensive patients with type 2 diabetes.

BACKGROUND AND AIM: Endothelial dysfunction in hypertensive type-2 diabetic patients is associated with increased levels of circulating soluble adhesion molecules (SAM). SAM participate in the development of diabetic macroangiopathy and microangiopathy. The aim of this study was to compare the effect of trandolapril (T) and its fixed-dose combination with verapamil (FDTV) on SAM levels in hypertensive type-2 diabetic patients. METHODS: Forty type-2 diabetic patients with never-treated hypertension were randomly assigned to two groups. One group (FDTV) received 2/180 mg once a day; the other group received T 2 mg once a day. Study drugs were administered for three months in both groups. VCAM-1, ICAM, and E-selectin were measured by ELISA at the beginning and end of the study. Patients were evaluated monthly for blood pressure, fasting serum glucose, and adverse events. Statistical analysis was performed with ANOVA. RESULTS: Both therapeutics regimens reduced significantly the levels of the SAM tested. When both groups were compared, we did not find a significant difference in ICAM and E-selectin reduction. However, VCAM-1 presented a significantly greater reduction (p = 0.022) in the trandolapril-verapamil group. No patient suffered adverse events. CONCLUSION: Our results show that FDTV produces a greater reduction of VCAM-1 circulating levels than trandolapril alone. This may explain some of the beneficial effects of this fixed dosed combination that are non-related to its antihypertensive effects.

[Levels of soluble adhesion molecules among normal and hypertensive type 2 diabetic patients]. / Niveles de moléculas de adhesión solubles en pacientes diabéticos tipo 2 normotensos e hipertensos.

BACKGROUND: Hypertension and type-2 diabetes affect endothelial function, which in turn increases the expression of soluble adhesion molecules and lead to the development of vascular damage. The aim of this study was to assess soluble adhesion molecule levels among normotensive and hypertensive diabetic patients. MATERIAL AND METHODS: Serum levels of soluble VCAM1, ICAM1 and e-selectin were measured in 80 type-2 diabetic patients, (40 normotensive and 40 hypertensive), and in 40 normotensive non-diabetic subjects by ELISA (RyDSystems Minneapolis). Statistical analysis was performed with ANOVA. RESULTS: Among diabetic patients, levels of all three soluble adhesion molecules were significantly increased when compared with non-diabetic patients (p < 0.001 for all three molecules), In diabetic hypertensive patients, higher levels of ICAM1 were detected in comparison to normotensive diabetic patients (316 vs. 295 ng/ml p < 0.01), VCAM1 and e-selectin levels were not different between diabetic patients with and without hypertension. CONCLUSIONS: Diabetes is associated with increased levels of soluble adhesion molecules, suggesting a role of these molecules may play in endothelial damage. ICAM1 is further increased when hypertension and diabetes are present. The latter may explain why diabetic-hypertensive patients displayed more complications than normotensive patients.

Niveles de moléculas de adhesión solubles en pacientes diabéticos tipo 2 normotensos e hipertensos / Levels of soluble adhesion molecules among normal and hypertensive type 2 diabetic patients

Antecedentes: La diabetes mellitus tipo 2 y la hipertensión arterial cursan con disfunción endotelial, lo que condiciona inflamación vascular, expresión de moléculas de adhesión que favorecen la migración celular subendotelial y el desarrollo de aterosclerosis. El objetivo de este estudio fue valorar los niveles circulantes de moléculas de adhesión solubles en pacientes diabéticos tipo 2 normotensos e hipertensos. Material y métodos: Las concentraciones en suero de VCAM1, ICAM1 y E-selectina fueron determinados por ELISA (RyDSystems Minneapolis), en 80 pacientes diabéticos tipo 2, (40 normotensos y 40 hipertensos), así como en 40 sujetos normotensos no diabéticos; el método estadístico empleado fue ANOVA. Resultados: Los pacientes diabéticos presentaron niveles significativamente mayores de moléculas de adhesión celular que los no diabéticos (p<0.001 para las tres moléculas). A su vez, entre los pacientes diabéticos, los sujetos hipertensos mostraron niveles significativamente mayores de ICAM que los normotensos (316±17 versus. 295±16 ng/ml p<0.01), mientras que en VCAM y E-selectina no hubo diferencia significativa. Conclusiones: Los pacientes diabéticos muestran niveles significativamente mayores de moléculas de adhesión solubles que los no diabéticos. La coexistencia de hipertensión aumenta significativamente los valores de ICAM, esto podría explicar la mayor frecuencia de complicaciones en los pacientes que cursan con las dos patologías.

BACKGROUND: Hypertension and type-2 diabetes affect endothelial function, which in turn increases the expression of soluble adhesion molecules and lead to the development of vascular damage. The aim of this study was to assess soluble adhesion molecule levels among normotensive and hypertensive diabetic patients. MATERIAL AND METHODS: Serum levels of soluble VCAM1, ICAM1 and e-selectin were measured in 80 type-2 diabetic patients, (40 normotensive and 40 hypertensive), and in 40 normotensive non-diabetic subjects by ELISA (RyDSystems Minneapolis). Statistical analysis was performed with ANOVA. RESULTS: Among diabetic patients, levels of all three soluble adhesion molecules were significantly increased when compared with non-diabetic patients (p < 0.001 for all three molecules), In diabetic hypertensive patients, higher levels of ICAM1 were detected in comparison to normotensive diabetic patients (316 vs. 295 ng/ml p < 0.01), VCAM1 and e-selectin levels were not different between diabetic patients with and without hypertension. CONCLUSIONS: Diabetes is associated with increased levels of soluble adhesion molecules, suggesting a role of these molecules may play in endothelial damage. ICAM1 is further increased when hypertension and diabetes are present. The latter may explain why diabetic-hypertensive patients displayed more complications than normotensive patients.

Correlation between circulating adhesion molecule levels and albuminuria in type 2 diabetic normotensive patients.

BACKGROUND: Endothelial dysfunction is a common feature in type 2 diabetic patients and is associated with inflammation, increased levels of circulating soluble adhesion molecules, and urinary albumin excretion. The aim of this study was to evaluate the role of circulating soluble adhesion molecules in the development of albuminuria. MATERIAL/METHODS: Thirty normotensive type-2 diabetic patients and 30 non-diabetic normotensive subjects were studied. VCAM-1, ICAM-1, and E-selectin were measured by ELISA and 24-h urinary albumin excretion was also measured (nephelometry). Relationships between the levels of circulating adhesion molecules and albuminuria were examined with Spearman's correlation coefficient. Statistical analysis was performed with ANOVA. RESULTS: It was found that diabetic patients have significantly (p<0.001) higher levels of circulating soluble adhesion molecules than control subjects. When levels of circulating soluble adhesion molecules were correlated with albuminuria, a significant correlation was found between VCAM-1 levels and 24-h urinary albumin excretion. CONCLUSIONS: These results suggest that VCAM-1 may be a marker of nephropathy in normotensive type 2 diabetic patients.

Efficacy of a fixed-dose combination of trandolapril-verapamil in obese hypertensive patients resistant to monotherapy.

This paper sought to determine if the fixed-dose combination of trandolapril and verapamil is effective in the treatment of hypertensive obese patients resistant to monotherapy. Thirty-six hypertensive obese patients uncontrolled by monotherapy were given the combination of trandolapril-verapamil (2/180 mg) for 12 weeks. Before and after taking the drug, they self-measured their blood pressure. Patients experienced a significant reduction of blood pressure (from 178 +/- 18/100 +/- 12 mm Hg to 135 +/- 14/76 +/- 7 mm Hg, p < 0.001). Eighty percent of patients reached therapeutic goals; one patient suffered from headaches and one had constipation. it was determined that the combination of trandolapril-verapamil is effective and safe for the management of hypertension in obese patients uncontrolled by monotherapy.

Importancia de la enzima convertidora de angiotensina (ECA) en la circulación coronaria / Importance of angiotensin converting enzyme in coronary circulation

A nivel cardiovascular, se sugiere que la síntesis de angiotensina II por la enzima conversora de angiotensina es secundaria a otras vías como la de la quimasa. En este estudio valoramos la importancia de la enzima conversora de angiotensina en la circulación coronaria durante el desarrollo de hipertensión. Se estimularon corazones de ratas normales (n = 4), hipertensas (n = 4) e hipertensas tratadas con ramipril (n = 4), en un sistema de perfusión tipo Langendorff. La angiotensina II produjo vasoconstricción coronaria dependiente de la concentración, y el efecto fue mayor en corazones de ratas hipertensas comparado con ratas normotensas (p < 0.05). La angiotensina I también produjo vasoconstricción y el efecto fue mayor en corazones de ratas hipertensas en comparación a la respuesta de ratas normotensas (p < 0.05). El ramiprilat inhibió 78 por ciento de la vasoconstricción inducida por angiotensina I en corazones de ratas normotensas y 82 por ciento en ratas hipertensas (p < 0.05). El bloqueo de la enzima conversora de angiotensina in vivo, potenció el efecto vasoconstrictor de la angiotensina I en corazones de ratas normotensas e hipertensas (p < 0.05). El efecto inhibitorio del ramiprilat disminuyó significativamente (p < 0.05) cuando se bloquearon los receptores de bradicinina. En conclusión, la síntesis de angiotensina II en corazones de ratas normotensas e hipertensas depende prioritariamente de la enzima conversora de angiotensina. La inhibición de la enzima conversora de angiotensina in vivo pudiera inducir otras vías que generan angiotensina II y posiblemente la actividad de bradicinina determina parcialmente el efecto de la inhibición de la enzima conversora de angiotensina a nivel coronario.